DESCRIPTION: With the increase in the average age of the population, there has been an increase in the number of people with balance disorders. Along with this occurrence has been an increasing awareness of the importance of the vestibular system for human well being. Our understanding of vestibular disorders is generally limited by a lack of knowledge about the function of the vestibular system. Foundational to the function of any system is its underlying chemical composition. For a part of the nervous system, this includes the chemistry of intracellular communication, via neurotransmitters, as well as the chemistry of energy metabolism and cell structure. One way to gain insight about a system is to look at its response to injury. This is of particular interest for the vestibular system because of its plasticity observed in clinical situations. It is well known that destruction of the peripheral vestibular sense organ leads immediately to total loss of the ability to maintain balance, but that over time the function returns. Despite much study, of this phenomenon, the underlying mechanisms remain unknown. It is our belief that a lack of systematic chemical information about the vestibular system seriously impairs reaching an understanding of vestibular compensation. We have therefore undertaken a detailed systematic study of the chemistry of the vestibular system and its changes during vestibular compensation. The major focus of the study is the vestibular nuclear complex because of its pivotal position in all vestibular function. A secondary focus is the vestibulocerebellum because of its close relation to the vestibular complex and likely role in at least some aspect's of vestibular compensation. We have been studying amino acid chemistry, which is critical for normal brain function and includes probably the major neurotransmitters of the brain, glutamate and y-aminobutyrate (GABA). There is increasing evidence that these two transmitters have important functions in the vestibular nuclear complex. Our methods include measurement of amino acid concentrations and related enzyme activities in the vestibular nuclear complex, immunohistochemistry and receptor binding autoradiography for glutamate receptors, and pharmacology of glutamate and GABA receptors, combined with a surgical lesioning strategy in rats.